BackgroundPrevious studies have suggested an effect of high arsenic concentration on cognitive and neurobehavioral function in humans.ObjectiveOur goal was to identify demographic and nutritional factors that are associated with As exposure and the influence of this exposure on cognitive function in school-age children.MethodsWe recruited 602 children 6–8 years of age living within 3.5 km of a metallurgic smelter complex in the city of Torreón, Mexico, to participate in a cross-sectional evaluation. Of these, 591 had complete anthropometry, iron, and zinc status by biochemical measurements in serum, blood lead concentration (PbB), and arsenic in urine (UAs), and 557 completed several cognitive performance tests.ResultsThe mean for UAs was 58.1 ± 33.2 μg/L; 52% of the children had UAs concentrations > 50 μg/L, and 50.7% of children had PbB ≥10 μg/dL. UAs concentration was associated with low socioeconomic status. Nutritional status indicators were not related to UAs concentrations. Linear and logistic regressions adjusted for hemoglobin concentration, PbB, and sociodemographic confounders showed a significant inverse association between UAs and Visual–Spatial Abilities with Figure Design, the Peabody Picture Vocabulary Test, the WISC-RM Digit Span subscale, Visual Search, and Letter Sequencing Tests (p < 0.05). Boys excreted significantly more UAs (p < 0.05) and were affected on different cognitive areas than girls.ConclusionsChildren living in an area contaminated with both As and lead showed that As contamination can affect children’s cognitive development, independent of any effect of lead.

Chronic exposure to inorganic arsenic (iAs) has been associated with increased risk of various forms of cancer and of noncancerous diseases. Metabolic conversions of iAs that yield highly toxic and genotoxic methylarsonite (MAsIII) and dimethylarsinite (DMAsIII) may play a significant role in determining the extent and character of toxic and cancer-promoting effects of iAs exposure. In this study we examined the relationship between urinary profiles of MAsIII and DMAsIII and skin lesion markers of iAs toxicity in individuals exposed to iAs in drinking water. The study subjects were recruited among the residents of an endemic region of central Mexico. Drinking-water reservoirs in this region are heavily contaminated with iAs. Previous studies carried out in the local populations have found an increased incidence of pathologies, primarily skin lesions, that are characteristic of arseniasis. The goal of this study was to investigate the urinary profiles for the trivalent and pentavalent As metabolites in both high- and low-iAs–exposed subjects. Notably, methylated trivalent arsenicals were detected in 98% of analyzed urine samples. On average, the major metabolite, DMAsIII, represented 49% of total urinary As, followed by DMAsV (23.7%), iAsV (8.6%), iAsIII (8.5%), MAsIII (7.4%), and MAsV (2.8%). More important, the average MAsIII concentration was significantly higher in the urine of exposed individuals with skin lesions compared with those who drank iAs-contaminated water but had no skin lesions. These data suggest that urinary levels of MAsIII, the most toxic species among identified metabolites of iAs, may serve as an indicator to identify individuals with increased susceptibility to toxic and cancer-promoting effects of arseniasis.

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Large interindividual variability in urinary arsenic profiles, following chronic inorganic arsenic exposure, is well-known in humans. To understand this variability, we studied the relationship between polymorphisms in the gene for human monomethylarsonic acid (MMA(V)) reductase/hGSTO1 and the urinary arsenic profiles of individuals chronically exposed to arsenic in their drinking water. To ensure that we did not overlook rare polymorphisms, not included in the public databases, we amplified and sequenced all six exons of the gene and their flanking regions, using DNA isolated from peripheral blood samples of 75 subjects, living in the vicinity of Torreon, Mexico. Four groups, based on the levels of arsenic (9-100 microg/L) in their drinking water, were studied. We identified six novel polymorphisms and two reported previously. The novel polymorphisms were a three base pair deletion (delGGC) in the first intron; a G> C transversion, leading to a serine-to-cysteine substitution at amino acid 86; a G > T transversion and a A > T transversion in intron 5; a G > A transition resulting in glutamate-to-lysine substitution in amino acid 208; and a C > T transition producing an alanine-to-valine substitution in amino acid 236. Two subjects displayed significant differences in patterns of urinary arsenic; they had increased levels of urinary inorganic arsenic and reduced levels of methylated urinary arsenic species as compared to the rest of the study population. These two subjects had the same unique polymorphisms in hGSTO1 in that they were heterozygous for E155del and Glu208Lys. The identified SNPs may be one of the reasons for the large interindividual variability in the response of humans to chronic inorganic arsenic exposure. The findings suggest the need for further studies to identify unambiguously specific polymorphisms that may account for interindividual variability in the human response to chronic inorganic arsenic exposure.

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DNA damage and DNA repair ability by means of the comet assay and the hydrogen peroxide challenge in lymphocytes from 65 children exposed simultaneously to As and Pb in Region Lagunera, Mexico. The first exposure scenario was concerned with natural As contamination in drinking water affecting all children, particularly those attending the schools farthest from (Gomez Palacio) and closest to the smelter (Pedro Garcia). The second scenario related to additional Pb and As soil and dust contamination in the schools located in the smelter vicinity (Heroe de Nacozari and Pedro Garcia). Most children (93%) had As in urine (AsU) above 50 microg/L and 65% had blood Pb (PbB) above 10 microg/dL. The highest AsU median levels were observed in the school farthest from the smelter, whereas the highest PbB values were observed in the closest school. DNA damage and a decreased repair ability observed in children attending the schools were more severe than those reported for healthy Mexican children. However, the multivariate analysis did not show significant associations between DNA basal damage and PbB or AsU. Lymphocytes from 58% of the children did not respond to the peroxide challenge, and those had a more severe basal DNA damage. DNA repair capacity showed a slowed response and was negatively associated with AsU. Thus, in addition to reduced exposure, further studies are needed to ascertain if the deficiency in DNA repair is transient or if children are already displaying a mutator phenotype and are at risk of developing cancer.

The prenatal period represents a critical window of susceptibility to inorganic arsenic (iAs) exposure from contaminated drinking water. Ingested iAs undergoes hepatic methylation generating mono and di-methyl arsenicals (MMAs and DMAs, respectively), a process that facilitates urinary arsenic (As) elimination. Differences in pregnant women's metabolism of As as indicated by greater proportions of MMAs and smaller proportions of  DMAs in urine are a risk factor for adverse birth outcomes. One carbon metabolism (OCM), the nutritionally-regulated pathway essential for supplying methyl groups, plays a role in As metabolism and is understudied during the prenatal period. In this cross-sectional study from the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gómez Palacio, Mexico, we assessed the relationships among OCM indicators (e.g. maternal serum B12, folate, and homocysteine (Hcys)), and levels of iAs and its metabolites in maternal urine and in neonatal cord serum. The prevalence of folate sufficiency (folate levels > 9 nmol/L) in the cohort was high 99%, and hyperhomocysteinemia (Hcys levels > 10.4 μmol/L) was low (8%). However, 74% of the women displayed a deficiency in B12 (serum levels < 148 pmol/L). Association analyses identified that infants born to mothers in the lowest tertile of serum folate had significantly higher mean levels of %MMA in cord serum relative to folate replete women. In addition, elevated maternal Hcys was associated with total As in maternal urine and cord serum as well as cord serum %MMAs. The results from this study indicate that maternal OCM status may influence the distribution of As metabolites in cord serum.